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Thyroid Disease Facts

Includes: Graves Disease, Toxic Goiter, Thyroiditis, and Excessive Thyroxine Ingestion ... Intestinal diseases: celiac disease, inflammatory bowel disease, short bowel ...

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Thyroid Disease Facts

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  1. Thyroid Disease Facts Jeffrey Medland Lt Col, USAF, MC, SFS Chief, Endocrinology MGMC, Andrews AFB, MD Capital Conference-June 2007

  2. Outline • Thyroid Testing • Hypothyroidism • Causes • Signs/symptoms • Treatment • Hyperthyroidism • Causes • Signs/symptoms • Treatment • Thyroid Nodules/ Cancer • Thyroid Disease and Pregnancy • Hypothyroidism • Hyperthyroidism (Hyperemesis Gravidarum, Graves’) • Thyroiditis • Factors affecting Thyroid function, LT4

  3. Thyroid Apical Membrane Colloid Basal Membrane

  4. Thyroid Peroxidase (TPO) “Coupling Reaction” “Iodination Reaction”

  5. Thyroid Testing • TSH • Best test for screening for thyroid dysfunction! • Log/linear response w/ FT4 • A 2-fold change in FT4 produces a 100-fold change in TSH • Not specific for a particular thyroid disease. • Don’t use TSH alone for diagnosis! • Also useful in • Assessing LT4 tx in 1° hypothyroidism • Monitoring TSH-suppressive tx in thyroid Ca

  6. Thyroid Testing • FT4 • Testing methods: • Equilibrium dialysis • Analog assays • Abnormal TSH check this next • Indications: • In conjunction w/ TSH for diagnosing hyperthyroidism or hypothyroidism. • Monitoring LT4 replacement in central hypothyroidism (TSH not helpful) • Assessing response to tx following 131-RAIA (Graves, toxic nodules) • Monitoring ATD tx in pregnant females • FT3 • Abnormal TSH + normal FT4, then check this (T3 Thyrotoxicosis)

  7. Overview of Thyroid Function Tests

  8. Thyroid Testing • Thyroid Antibodies (TPO, Tg, TSI, TRAb) • TPO • TPO + Tg Ab’s assoc w/ Hashimoto’s. TPO more sensitive. • Helpful in predicting those w/ subclinical hypothyroidism who are at ↑ risk for progression to overt hypothyroidism. • TSI • When dx of Graves’ in question • Note: a negative test does not r/o Graves’ • Pregnant women w/ Graves’ • to determine fetal risk of thyroid dysfunction (due to transplacental passage of stimulating or blocking Ab’s). • Suspected euthyroid ophthalmopathy. • In pt’s w/ alternating hyper- and hypothyroidism (due to fluctuations in TSH receptor stimulating and blocking and stimulating Ab’s) • Thyroglobulin (Tg) • Indications • Thyroid cancer recurrence • Factitious (exogenous) vs. endogenous hyperthyroidism • Note: Most assays are not reliable in pt’s (+) for anti-Tg Ab • Interferes w/ method of Tg measurement (causing factitious low Tg)

  9. Thyroid Testing • Radioactive Iodine Uptake and Scan (RAIU/Scan) • 123-RAIU/Scan or 131-RAIU/Scan • Indications: • biochemically hyperthyroid pt • No role in euthyroid or hypothyroid pt’s • RAIU produces a number. • 4-hr (normal 10-15%) • 24-hr (normal 20-30%) • The scan produces a picture • Tc99m-Pertechnetate Scan • Picture only, no number

  10. Thyroid Testing • Fine Needle Aspiration (FNA) • provides the most direct information about a thyroid nodule • 95% sensitivity • Ultrasound • to assess thyroid nodule size and characteristics (cystic vs. solid) • often used to guide FNA’s • Calcitonin • h/o MTC • Thyroid nodule and (+) FHx of MTC (Familial, MEN2A, MEN2B) • MEN2A: MTC, HyperPTH, Pheo • MEN2B: MTC, Pheo, Mucosal neuromas

  11. F-15D

  12. Hypothyroidism • More common than hyperthyroidism • 99% is primary (< 1% due to TSH deficiency) • Hashimoto’s • most common thyroid problem (4% of population) • most common cause in iodine-replete areas • aka chronic lymphocytic thyroiditis • Assoc w/ TPO Ab’s (90%), less commonly Tg Ab’s. • Iatrogenic Hypothyroidism from 131-RAIA (following tx for Graves’) • Postpartum (silent) thyroiditis • Silent/painless • Occurs within 6 weeks6 months postpartum • Incidence: 10-15% of all women, ≈ 25% women w/ Type 1 DM • Up to 50% are TPO Ab (+) • 70% chance of recurrence w/ subsequent pregnancies

  13. Hypothyroidism • Subacute thyroiditis • aka de Quervain’s, Granulomatous • Painful, often radiates to the ear • c/o malaise, pharyngitis, fatigue, fever, neck pain/swelling • Viral etiology (URI/ pharyngitis) • self-limited. Can tx inflammation w/ ASA, NSAID’s or steroids • Suppurative/ Acute Infectious Thyroiditis • Infections of the thyroid are rare • normally protected from infection by its thick capsule • Bacterial >> fungal, mycobacterial or parasitic • Pt’s are acutely ill w/ a painful thyroid gland • assoc w/ fever/chills, anterior neck pain/swelling, dysphagia and dysphonia

  14. Thyroiditis Stage 1 Stage 2 Stage 4 Stage 3 • Clinical Course of Painful Subacute Thyroiditis, Painless Postpartum Thyroiditis, • and Painless Sporadic Thyroiditis. • Measurements of serum thyrotropin (TSH), Thyroxine(T4) and iodine-123 (123I) • uptake show thyrotoxicosis during the first three months, followed by • hypothyroidism for three months and then by euthyroidism.

  15. Hypothyroidism • Reidel’s Struma/Thyroiditis (rare) • Pt’s present w/ a painless, hard, fixed goiter • hypothyroidism occurs when entire gland becomes fibrosed • can see fibrosis of other tissues (fibrosing retroperitonitis, orbital fibrosis, or sclerosing cholangitis) • Drug-induced • Amiodarone • Lithium • Interferon-alpha • Interleukin-2 • Iodine deficiency • Most common cause of hypothyroidism worldwide!!

  16. Hypothyroidism • Symptoms • General Slowing Down • Lethargy/somnolence • Depression • Modest Weight Gain • Cold Intolerance • Hoarseness • Dry skin • Constipation (↓ peristaltic activity) • General Aches/Pains • Arthralgias or myalgias (worsened by cold temps) • Brittle Hair • Menstrual irregularities • Excessive bleeding • Failure of ovulation • ↓ Libido

  17. Hypothyroidism • Exam: • Dry, pale, course skin w/ yellowish tinge • Periorbital edema • Puffy face and extremities • Sinus Bradycardia • Diastolic HTN • ↓ Body Temperature • Delayed relaxation of DTRs • Megacolon (↓ peristaltic activity) • Pericardial/ pleural effusions • CHF • Myxedema (nonpitting edema) • Bradycardia and hypothermia- think hypothyroidism!

  18. Hypothyroidism • Laboratory Findings • Elevated TSH • Low FT4 • TPO Ab (+) • Pregnant women w/ TPO Ab (+) • Miscarriage rate doubles • ↑ risk post partum thyroiditis (35%) • mild anemia • ↑ CPK-MB • ↑ LDL,↑Chol (↓lipid clearance) • Hyponatremia

  19. Hypothyroidism (Treatment) Synthroid (LT4) • Initial starting dosage 1.6 mg/kg/day. • Dose correlates better w/ lean body wt • ≈ 80% of PO dose of LT4 is absorbed • vs. Cytomel which is 95% absorbed • The main absorptive sites proximal and mid-jejunum. • Food can ↓ LT4 absorption up to 40-50%. • Serum LT4 levels rise 10-15% after ingestion, peaking at 2-4 hrs. • Serum LT3 levels don’t change due to the slow peripheral conversion of T4  T3. • T-1/2 LT4 is 7 days • can be given weekly in non compliant pt’s. • Goal LT4 replacement: TSH 1.0-2.5 mU/L

  20. Hypothyroidism (treatment in general) Indications for LT4 replacement • Asymptomatic: TSH > 10 • Asymptomatic and TPO Ab (+): TSH > 5 • Symptomatic: TSH > 5 • Pregnant female: TSH > 5 • Goitrous: TSH > 5

  21. Hypothyroidism (treatment in general) Hypothyroidism + surgery • Postpone elective surgery in any hypothyroid pt until the euthyroid state is restored, however • Urgent surgery should not be postponed in hypothyroid pt’s, • though potential complications should be watched for. Hypothyroidism + elderly • It is prudent to begin treatment with low dose LT4, starting at 12.5 or 25 mcg/day • Titrate to goal or less than goal if cardiac symptoms develop despite max anti-anginal tx.

  22. Hypothyroidism (treatment in general) Combined LT4/LT3 tx • Bottom Line: • most studies show combination T4/T3 therapy does not appear to be superior to LT4 alone, for the management of hypothyroid symptoms. • If you decide to try combined T4/T3 therapy • ↓ LT4 by 50 mcg and add 12.5 mcg LT3 (cytomel) in the a.m. • ↓ LT4 by 12.5-25 mcg, and add 5 mcg LT3 in the a.m. • Check TSH before LT3 dose • T-1/2 Cytomel is 1 day

  23. Hyperthyroidism • Thyrotoxicosis = “any condition that results in thyroid hormone excess” • Includes: Graves Disease, Toxic Goiter, Thyroiditis, and Excessive Thyroxine Ingestion • Hyperthyroidism = “Specifically hyperfunctioning of the thyroid gland” • Most Commonly caused by Graves Disease in the young • Toxic Nodular Goiter in the elderly

  24. Hyperthyroidism • Graves’ Disease • Due to autoAb’s directed against the TSH receptor, resulting in continuous stimulation of the thyroid gland to secrete hormone. • Ab’s to TSH receptor (+) in ≈ 80% of Graves’ pt’s • Ab’s to TPO or Tg are (+) in ≈80% of Graves’ pt’s • Female:Male (5-10:1) • Caucasian = Asian > Black • Toxic MNG • Generally arises in the setting of a long-standing MNG • More common in the elderly, areas of iodine deficiency • Toxic Adenoma (Plummer’s Disease) • More common in women, areas of iodine deficiency • adenomas > 3 cm are more prone to overt hyperthyroidism

  25. Hyperthyroidism • Iodine-induced Hyperthyroidism (jod-basedow phenomenom) • Amiodarone-induced (AIT Type 1) • IV Contrast • Diets high in iodine • Thyroiditis • Subacute (de Quervains) • painful • Postpartum • painless • Suppurative • painful • Amiodarone-induced (AIT Type 2)

  26. Hyperthyroidism • Symptoms • Jittery, shaky, nervous • Difficulty concentrating • Emotional lability • Insomnia • Rapid HR, palpitations, DOE • Feeling Hot • Weight Loss (can see weight gain) • Freq BMs (hyperdefecation, not diarrhea) • Fatigue • Menses w/ lighter flow, shorter duration

  27. Hyperthyroidism • Exam • Eye findings (20%) • Goiter • Thyroid bruit or thrill • Tachycardia: Sinus Tach, A-Fib • Flow murmur • Systolic Hypertension • Hyperreflexia • Tremors • UE, tongue • Proximal muscle weakness • Thenar/ hypothenar atrophy • Acropachy • Onycholysis (<1%) • separation of nail from the nailbed • Dermopathy (1%)

  28. Hyperthyroid Eye Disease • Hyperthyroidism (any cause) • Lid lag, lid retraction and stare • Due to increased adrenergic tone stimulating the levator palpebral muscles. • True Graves’ Ophthalmopathy • Proptosis • Diplopia • Inflammatory changes • Conjunctival injection • Periorbital edema • Chemosis • Due to thyroid autoAb’s that cross-react w/ Ag’s in fibroblasts, adipo-cytes, + myocytes behind the eyes.

  29. Hyperthyroid Eye Disease • Causes of Worsening Ophthalmopathy • Pre-existing eye disease • Smoking • marked ↑ T3 • marked ↑ TSI titers • Not letting pt get to hypothyroid state following 131-RAIA. Does131-RAIA worse ophthalmopathy? • Majority of cases arise in the 18 mos before to 18 mos after the onset of thyrotoxicosis. • Thus a fair number of cases can be ex-pected to coincide w/ timing of 131-RAIA. • Two prospective randomized trials have shown that 131-RAIA more likely (vs. other tx modalities) to worsen ophthalmopathy.

  30. Graves’ Dermopathy Thyroid Dermopathy • Thickening and redness of the dermis • Due to lymphocytic infiltration • Distribution • Pretibial (93.3%), • Pretibial+ feet (4.3%), • Pretibial + UE (1.1%).

  31. Graves’ Dermopathy Localized plaque on the outer aspect of the skin. Horny form over shin and dorsum of the foot

  32. Thyroid Acropachy Thyroid acropachy. This is most marked in the index fingers and thumbs.

  33. Hyperthyroidism • Laboratory Findings • TSH nearly undetectable • Elevated FT4 or FT3 • mild leukopenia, • N/N anemia, • ↑ LFT’s and alk phos, • mild ↑ Ca++, • ↓ albumin • ↓ chol

  34. RAIU/Scan Increased RAIU • Graves’ Disease • Toxic Nodules • MNG • Adenoma • hCG secreting tumors • Hydatidiform mole • Choriocarcinoma • TSH mediated thyrotoxicosis • Pituitary tumor • Pituitary resistance to thyroid hormone • Iodine Deficiency • RAIU produces a number. • 4-hr (normal 10-15%) • 24-hr (normal 20-30%) • The scan produces a picture.

  35. RAIU/Scan Decreased RAIU • Thyroiditis • Chronic painless • Postpartum • Subacute • Amiodarone-induced • Thyroiditis Factitia • Iodine Excess • Contrast dye • Diet • Amiodarone • Struma ovarii: (ectopic thyroid hormone production from thyroid tissue in an ovarian teratoma) • RAIU produces a number. • 4-hr (normal 10-15%) • 24-hr (normal 20-30%) • The scan produces a picture.

  36. Hyperthyroidism (Treatment) 1) β-blockers(symptom control) • Propranolol (Inderal ®) LA: 60-320 mg daily • Atenolol (Tenormin ®): 50-100 mg daily • Metoprolol (Lopressor ®): 50-100 mg bid • If β-blocker contraindicated then Verapamil (Calan ®) 40-80 mg tid 2) 131-RAIA(70% thyroidologists prefer) • Dosing • Graves: 10-15 mCi • Toxic MNG/Adenoma: 20-30 mCi • Absolute contraindications • Pregnancy and nursing moms (excreted in breast milk)! • Pregnancy should be deferred for at least 6 months following tx w/ 131-RAIA. • Prudent to avoid 131-RAIA in pt’s w/ active moderate severe Graves’ ophthalmopathy.

  37. Hyperthyroidism (Treatment) 3) Antithyroid Drugs(30% thyroidologists prefer) • Propylthiouracil (PTU) • 100 mg bid-tid to start • Tapazole (Methimazole) • 10X more potent the PTU • 10 mg bid-tid to start • Complications of ATD’s • Dose dependent w/ Tapazole, Idiosyncratic w/ PTU. • Agranulocytosis (1/200-500) • usually presents w/ acute pharyngitis/ tonsilitis or pneumonia. • Rash • Hepatic necrosis w/ PTU, Cholestatic jaundice w/ Tapazole. • Arthralgias

  38. Hyperthyroidism (Treatment) 3) Antithyroid Drugs(30% thyroidologists prefer) • Candidates for ATD’s • Children and adolescents • Pt’s w/ moderate severe ophthalmopathy • Thyroid Storm • Pt’s w/ mild disease: small goiter, low titers of TSI (TSH-R Ab), low maintenance dose • Pt’s w/ severe disease prior to 131-RAIA • stop ATD’s 5-7 days prior to 131-RAIA • Labs • Follow TSH/FT4, CBC, LFT’s

  39. Hyperthyroidism (Treatment) 4) Surgery(sub-total thyroidectomy) • Indications • Pt preference • Pregnant women w/ failed ATD’s • Large or symptomatic goiters • When there is question of malignancy • Need to be euthyroid prior to surgery • To ↓ the risk of arrhythmias during induction of anesthesia • To ↓ the risk of thyroid storm post operatively • ATD’s + β-blockers • Risks • Permanent hypoparathyroidism • Recurrent laryngeal nerve problems • Permanent hypothyroidism

  40. Hyperthyroidism Apathetic Hyperthyroidism • Elderly pt’s w/ Graves' disease may present w/ apathy, weight loss, muscular weakness, arrhythmias (esp A-fib), CHF, + constipation. • A goiter may not be palpable in as many as 70% of pt’s • There symptoms may suggest PMR or depression • The usual hyperkinetic signs and symptoms seen in Graves’ are not typically present in the elderly. • Check all elderly w/ new-onset atrial arrhythmias or CHF for hyperthyroidism

  41. Hyperthyroidism Thyroid Storm • A life-threatening condition characterized by an exaggeration of the manifestations of thyrotoxicosis • Diagnostic Criteria (based on point system) • Thermoregulatory Dysfunction: ↑ Temp (99°>104°) • CNS: +/-, mild (Agitation)/mod (delirium)/severe (seizures, coma) • Tachycardia: (99>140 bpm) • CHF: +/-, mild (edema)/mod (rales)/severe (pulm edema) • Atrial Fibrillation: +/- • Precipitant History • Treatment • ATD’s (PTU, Tapazole) • Iodide (Lugol’s solution) • β-blockers • Corticosteroids • Avoid ASA • Definitive Tx when euthyroid: 131-RAIA or surgery

  42. Subclinical Hyperthyroidism • Refers to an elevation in T4 and/or T3 within the normal range, leading to suppression of the pituitary secretion of TSH in the subnormal range (i.e. normal T4 and T3, low TSH). • Clinical symptoms and signs are frequently absent or nonspecific. • Usually found in the elderly • Often due to an autonomously functioning MNG or adenoma. • Studies have linked subclinical thyrotoxicosis to • Accelerated bone loss in postmenopausal women • A higher incidence of atrial dysrhythmias (esp atrial fibrillation) • Recent studies suggest an increase in cognitive impairment and all-cause mortality (esp CV disease). • A TSH below the lower limit of normal, but above 0.1 mIU/mL are less likely to result in such complications. • If pt’s are not treated, then careful f/u.

  43. Thyroid Nodules • Structural disorders of the thyroid (i.e. nodules- simple or multiple) are more common than functional disorders. • Prevalence • Palpable: 5% • Non-Palpable: 40-50% • Cancer in nodules: 5% • Risks • Women > Men • Smoking • h/o XRT to head/neck (esp children) • Iodine deficiency • Most are Euthyroid and Asymptomatic • Less than 1% with thyrotoxicosis

  44. Thyroid Nodules Red Flags concerning for Cancer • Male • Extremes of age (<20 or >60) • Rapid Growth • > 4 cm • Symptoms of local invasion • hoarseness, dysphagia • h/o XRT to the head/neck (esp children) • Family history of Thyroid Ca • (PTC or MTC) • Hard, fixed lesion • (+) LN • h/o familial adenomatous polyposis

  45. Thyroid Nodules FNA Results: • Benign (69%) • f/u 6-12 months • Surgery if • MNG w/ compressive Symptoms • Growth of Nodule • Recurrence of cystic nodule after aspiration • Insufficient (17%) • Repeat FNA 3-4 months • Indeterminate/ Suspicious (10%) • follicular neoplasm • 85% benign adenomas • 123-RAIU/Scan • Surgery • Malignant (5%) • Surgery • 131-RAIA if PTC or FTC

  46. Thyroid Nodules “Mimickers” • Thyroid Hemiagenesis • Agenesis of one lobe of the thyroid, w/ hypertrophy of the other presenting as a mass in the neck mimicking a nodule. • Occurs in 1/2500 people • Usually the left lobe that fails to develop w/ hypertrophy in the right lobe. • 95% of the time • Parathyroid gland • Thyroglossal duct remnants

  47. Thyroid Cancer • Papillary Thyroid Ca (PTC): 75% • Follicular Thyroid Ca (FTC): 15-20% • Medullary Thyroid Ca (MTC): < 5% • Anaplastic: < 5 % • Lymphoma: rare • Hashimoto’s is a risk factor • Metastatic to thyroid: rare • Breast, Renal cell, melanoma and lung Ca MTC • FMTC • MEN2A • MTC, HyperPTH, Pheo • MEN2B • MTC, Pheo, Mucosal neuromas

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